Cyclosporine A Induces Cardiac Developmental Toxicity in Zebrafish by Up-Regulation of Wnt Signaling and Oxidative Stress

Due to the widely application of Cyclosporine A (CsA) as an immunosuppressant in clinic, it is necessary to study its potential toxicity. Therefore, we used zebrafish as a model animal to evaluate the toxicity of CsA on embryonic development. Exposure of zebrafish embryos to CsA at concentrations of...

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Main Authors: Mengqi Wan (Author), Ling Huang (Author), Jieping Liu (Author), Fasheng Liu (Author), Guilan Chen (Author), Huiwen Ni (Author), Guanghua Xiong (Author), Xinjun Liao (Author), Huiqiang Lu (Author), Juhua Xiao (Author), Qiang Tao (Author), Zigang Cao (Author)
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Published: Frontiers Media S.A., 2021-11-01T00:00:00Z.
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100 1 0 |a Mengqi Wan  |e author 
700 1 0 |a Ling Huang  |e author 
700 1 0 |a Jieping Liu  |e author 
700 1 0 |a Fasheng Liu  |e author 
700 1 0 |a Guilan Chen  |e author 
700 1 0 |a Huiwen Ni  |e author 
700 1 0 |a Guanghua Xiong  |e author 
700 1 0 |a Xinjun Liao  |e author 
700 1 0 |a Huiqiang Lu  |e author 
700 1 0 |a Juhua Xiao  |e author 
700 1 0 |a Qiang Tao  |e author 
700 1 0 |a Zigang Cao  |e author 
245 0 0 |a Cyclosporine A Induces Cardiac Developmental Toxicity in Zebrafish by Up-Regulation of Wnt Signaling and Oxidative Stress 
260 |b Frontiers Media S.A.,   |c 2021-11-01T00:00:00Z. 
500 |a 1663-9812 
500 |a 10.3389/fphar.2021.747991 
520 |a Due to the widely application of Cyclosporine A (CsA) as an immunosuppressant in clinic, it is necessary to study its potential toxicity. Therefore, we used zebrafish as a model animal to evaluate the toxicity of CsA on embryonic development. Exposure of zebrafish embryos to CsA at concentrations of 5 mg/L, 10 mg/L, and 15 mg/L from 12 hpf to 72 hpf resulted in abnormal embryonic development, including cardiac malformation, pericardial edema, decreased heart rate, decreased blood flow velocity, deposition at yolk sac, shortened body length, and increased distance between venous sinus and arterial bulb (SV-BA). The expression of genes related to cardiac development was disordered, and the apoptotic genes were up-regulated. Oxidative stress level was up-regulated and accumulated in pericardium in a dose-dependent manner. Astaxanthin (ATX) treatment could significantly alleviate zebrafish heart defects. CsA induced up-regulation of Wnt signaling in zebrafish, and IWR-1, an inhibitor of Wnt signaling pathway, could effectively rescue the heart defects induced by CsA. Together, our study indicated that CsA induced cardiac developmental toxicity in zebrafish larvae through up-regulating oxidative stress and Wnt signaling, contributing to a more comprehensive evaluation of the safety of the drug. 
546 |a EN 
690 |a cyclosporine a 
690 |a cardiac toxicity 
690 |a oxidative stress 
690 |a wnt signaling 
690 |a apoptosis 
690 |a Therapeutics. Pharmacology 
690 |a RM1-950 
655 7 |a article  |2 local 
786 0 |n Frontiers in Pharmacology, Vol 12 (2021) 
787 0 |n https://www.frontiersin.org/articles/10.3389/fphar.2021.747991/full 
787 0 |n https://doaj.org/toc/1663-9812 
856 4 1 |u https://doaj.org/article/7655dadcd85841d0a724e67bbafe2ed6  |z Connect to this object online.